title: Role of pulsatility in hypothermic reconditioning of porcine kidney grafts by machine perfusion after cold storage.
abstract: BACKGROUND
  Brief in-house machine perfusion after cold storage (CS) (hypothermic reconditioning) has been proposed as a convenient tool to improve kidney graft function. The present study aimed to investigate the mechanistic role of vascular pulsatility in this context.
  
  
  METHODS
  Kidney function after cold preservation (4°C, 18 hr) and subsequent reconditioning by 90 min of pulsatile machine perfusion (PP) (30/20 mm Hg) or nonpulsatile machine perfusion (NPP) (30 mm Hg) was studied in an isolated kidney perfusion model in pigs (n=6 for both) and compared with simply CS grafts.
  
  
  RESULTS
  Compared with CS, PP but not NPP significantly improved renal perfusate flow and urine production and significantly increased the reduction of perfusate levels of creatinine and urea during reperfusion. Perfusate levels of fatty acid binding protein, a marker of tubular cell injury, were dramatically reduced by PP but not NPP. PP and NPP lowered fractional excretion of sodium, but significance was only reached for PP. Molecular effects of PP comprised a significant (vs. CS) mRNA elevation of the endothelial anti-inflammatory transcription factor Krüppel-like factor 2 as well as endothelial nitric oxide synthase, along with significantly higher perfusate levels of the endogenous vasodilator nitric oxide. Functional efficiency of PP over CS was confirmed in additional porcine transplant experiments (n=5 for both) by, for example, up to threefold improved clearance of creatinine during the first days after transplantation.
  
  
  CONCLUSIONS
  PP of 90 min shortly before transplantation seems to be an efficient mechanism to reduce proinflammatory endothelial phenotype and improve functional outcome of kidney grafts even after preceding static storage.
authors.affiliation: 1 Clinic of General, Visceral and Transplantation Surgery, University Hospital of Essen, Essen, Germany. 2 Surgical Research Division, University Clinic of Surgery, Bonn, Germany. 3 Address correspondence to: Prof. Thomas Minor, Dr. med., Surgical Research Division, University Clinic of Surgery, 53127 Bonn, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Gallinat
authors.forename: Mario
authors.initials: M
authors.lastname: Fox
authors.forename: Bastian
authors.initials: B
authors.lastname: Lüer
authors.forename: Patrik
authors.initials: P
authors.lastname: Efferz
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.forename: Thomas
authors.initials: T
authors.lastname: Minor
mesh_terms: D000818:Animals; D050377:Cold Ischemia; D003404:Creatinine / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D007036:Hypothermia, Induced; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009926:Organ Preservation / Q000009:adverse effects / Q000379:methods*; D010477:Perfusion / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D011673:Pulsatile Flow; D012333:RNA, Messenger / Q000378:metabolism; D020127:Recovery of Function; D012079:Renal Circulation; D012964:Sodium / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D020858:Tissue and Organ Harvesting / Q000009:adverse effects; D014508:Urea / Q000378:metabolism; D014563:Urodynamics; D057772:Vascular System Injuries / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D050556:Fatty Acid-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D009569:Nitric Oxide; D014508:Urea; D012964:Sodium; D003404:Creatinine; D052250:Nitric Oxide Synthase Type III